The effect of gastrectomy on regorafenib exposure and progression-free survival in patients with advanced gastrointestinal stromal tumours

Br J Clin Pharmacol. 2019 Oct;85(10):2399-2404. doi: 10.1111/bcp.14061. Epub 2019 Aug 19.


Aims: We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome.

Methods: Efficacy and pharmacokinetic data from 133 gastrointestinal stromal tumour patients included in a phase III trial were analysed. Patients were subdivided into 2 groups according to the extent of the gastrectomy (no/nonsignificant gastrectomy and major gastrectomy). Progression-free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure were measured.

Results: A total of 133 patient were included, of whom 27 underwent major gastrectomy. In patients with no/nonsignificant gastrectomy the median PFS was 145 (interquartile range 43-281) days. The PFS in patients with a major gastrectomy was 172 (interquartile range 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/nonsignificant gastric surgery. The average ± standard deviation total concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 ± 1.53 μmol/L and 6.7 ± 1.56 μmol/L in patient with major gastrectomy and no/nonsignificant gastrectomy respectively.

Conclusion: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in PFS between the subgroups was seen.

Keywords: gastrectomy; gastrointestinal stromal tumour; pharmacokinetics; regorafenib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Clinical Trials, Phase III as Topic
  • Female
  • Gastrectomy / methods*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Neoplasms / therapy*
  • Gastrointestinal Stromal Tumors / pathology
  • Gastrointestinal Stromal Tumors / therapy*
  • Humans
  • Male
  • Middle Aged
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / pharmacokinetics
  • Progression-Free Survival
  • Pyridines / administration & dosage*
  • Pyridines / pharmacokinetics
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib